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Pregnancy and Cardiovascular Disease become clinically evident until 10 to 20 years after treatment. Echocardiography may be repeated at therapy completion Dexrazoxane, an iron chelator, reduces the incidence of and at 6 to 12 months in asymptomatic patients at increased risk. anthracycline cardiotoxicity and should be considered for Currently, there are no guidelines for long-term suneillance of those at increased risk. Continuous anthracycline administra patients with normal LVEF after cardiotoxic chemotherapl: tion, as opposed to bolus, and liposomal formulations of In patients \vith clinical signs or symptoms of cardiac doxorubicin also should be considered to lower risk for dysfunction. measurement of cardiac biomarkers (e.g.' tro anthracycline toxicity. The use of ACE inhibitors, angiotensin ponin, N terminal pro-B type natriuretic peptide) and echo receptor blockers, and p-blockers to prevent cardiotoxicity is cardiographf including GLS are recommended in identiffing an ongoing area of interest, with conflicting results from small early toxicity and guiding individual therapy. At present. treat- studies. ment of patients with chemotherapy induced heart failure Reversible injury is more commonly associated with tar follows standard paradigms, and decisions regarding continu geted molecular therapy, such as trastuzumab, multitargeted ation of chemotherapy must be individualized. tyrosine kinase inhibitors, and anti vascular endothelial I(EY POIilTS growth factor antibodies. Trastuzumab toxicity causes Ieft ventricular (LV) systolic dysfunction, with symptoms of heart . Traditional cardiovascular risk factors increase the car diotoxic risk of chemotherapy and should be managed failure in 3'/" to 7"/,, of patients. It is more common in patients aggressively. older than 50 years and with concomitant anthracycline use. Multitargeted tyrosine kinase inhibitors also cause cardiotox- o Chronic anthracycline toxicity usually presents as irre icity, although not all tyrosine kinase inhibitors carry the same versible dilated cardiomyopathy. risk. Sunitinib is associated with up to a 50% incidence of new or o Cardiotoxicity from trastuzumab manifests as reversible worsened hypertension and up to a 15% incidence of decreased left ventricular systolic dysfunction. LV ejection fraction (LVEF). These effects may be reversible with early recognition. Bevacizumab, an anti-vascular endothelial growth factor antibody, is associated with significant but reversible hypertension. Pregnancy and In patients preparing to receive chemotherapy associated Card iovascu lar Disease with possible LV dysfunction, baseline echocardiography is recommended. Measurement of global longitudinal strain (GLS) Maternal mortality has increased in the United States while as part of surveillance echocardiography has been recom- decreasing in other Western countries o\er the past t$/o dec mended by some expert consensus panels. GLS expresses longi- ades. Acquired cardiovascular disorders (cardiomyopathy, tudinal myocardial shortening as a simple percentage and may coronary artery disease, aortic disorders) are the most com be more sensitive than other echocardiographic techniques in mon cause of maternal mofiality. detecting ear$ myocardial dysfunction. For patients in whom echocardiography is technically diffi cult, multigated acquisition and cardiac magnetic resonance imaging are alternatives. Card iovascu la r Cha nges Although the frequency of surveillance of asymptomatic During Pregnancy patients must be based on clinical judgment, it is reasonable to Knowledge of the cardiovascular changes of pregnancy is nec repeat echocardiography at a cumulative anthracycline dose of essary to distinguish betr,teen normal and pathologic signs and 250 mg/m2 and before each dose in patients with pre existing symptoms in the pregnant patient (Table 45). During a normal LV dysfunction or those receiving higher cumulative doses. pregnancy, patients develop a relative anemia due to increases The frequency of echocardiographic surveillance in patients in plasma volume and, to a lesser degree. erythrocyte mass. receiving trastuzumab who are at high risk for cardiac dys- Mean arterial pressure slightly decreases in the setting of function is based on clinical judgment. Trastuzumab is tempo reduced systemic vascular resistance and increased heart rate rarily stopped if the LVEF drops by more than 157, or drops and cardiac output. By the 32nd week ofpregnancy. maternal 10% to 15% and below the normal level. Patients who demon cardiac output peaks at approximately 407, to 50'X, above the strate normalization of LV function after discontinuation of prepregnancy level owing to increased heart rate and stroke trastuzumab may receive additional therapy, and retrospective volume. During delivery the cardiac output may increase to as data has shown that patients whose LVEF remains greater than much as BO'X, above the prepregnancy level. 50% may continue treatment without long term cardiac effects. A relative decline in GLS ofgreater than 15'7, is considered sub clinical LV dysfunction and should prompt consultation with a Prepreg na ncy Eval uation cardiologist. In patients taking sunitinib, surveillance with A1l women with cardiovascular disease should receive preg baseline N-terminal pro-B-type natriuretic peptide measure nancy counseling. If appropriate, women should receive ment and LVEF assessment at baseline, 1 month, and every genetic counseling and possibly testing. Women who are 3 months thereafter has been advocated. anticipating pregnancy should undergo multidisciplinary

become clinically evident until 10 to 20 years after treatment. Echocardiography may be repeated at therapy completion Dexrazoxane, an iron chelator, reduces the incidence of and at 6 to 12 months in asymptomatic patients at increased risk. anthracycline cardiotoxicity and should be considered for Currently, there are no guidelines for long-term suneillance of those at increased risk. Continuous anthracycline administra patients with normal LVEF after cardiotoxic chemotherapl: tion, as opposed to bolus, and liposomal formulations of In patients \vith clinical signs or symptoms of cardiac doxorubicin also should be considered to lower risk for dysfunction. measurement of cardiac biomarkers (e.g.' tro anthracycline toxicity. The use of ACE inhibitors, angiotensin ponin, N terminal pro-B type natriuretic peptide) and echo receptor blockers, and p-blockers to prevent cardiotoxicity is cardiographf including GLS are recommended in identiffing an ongoing area of interest, with conflicting results from small early toxicity and guiding individual therapy. At present. treat- studies. ment of patients with chemotherapy induced heart failure Reversible injury is more commonly associated with tar follows standard paradigms, and decisions regarding continu geted molecular therapy, such as trastuzumab, multitargeted ation of chemotherapy must be individualized. tyrosine kinase inhibitors, and anti vascular endothelial I(EY POIilTS growth factor antibodies. Trastuzumab toxicity causes Ieft ventricular (LV) systolic dysfunction, with symptoms of heart . Traditional cardiovascular risk factors increase the car diotoxic risk of chemotherapy and should be managed failure in 3'/" to 7"/,, of patients. It is more common in patients aggressively. older than 50 years and with concomitant anthracycline use. Multitargeted tyrosine kinase inhibitors also cause cardiotox- o Chronic anthracycline toxicity usually presents as irre icity, although not all tyrosine kinase inhibitors carry the same versible dilated cardiomyopathy. risk. Sunitinib is associated with up to a 50% incidence of new or o Cardiotoxicity from trastuzumab manifests as reversible worsened hypertension and up to a 15% incidence of decreased left ventricular systolic dysfunction. LV ejection fraction (LVEF). These effects may be reversible with early recognition. Bevacizumab, an anti-vascular endothelial growth factor antibody, is associated with significant but reversible hypertension. Pregnancy and In patients preparing to receive chemotherapy associated Card iovascu lar Disease with possible LV dysfunction, baseline echocardiography is recommended. Measurement of global longitudinal strain (GLS) Maternal mortality has increased in the United States while as part of surveillance echocardiography has been recom- decreasing in other Western countries o\er the past t$/o dec mended by some expert consensus panels. GLS expresses longi- ades. Acquired cardiovascular disorders (cardiomyopathy, tudinal myocardial shortening as a simple percentage and may coronary artery disease, aortic disorders) are the most com be more sensitive than other echocardiographic techniques in mon cause of maternal mofiality. detecting ear$ myocardial dysfunction. For patients in whom echocardiography is technically diffi cult, multigated acquisition and cardiac magnetic resonance imaging are alternatives. Card iovascu la r Cha nges Although the frequency of surveillance of asymptomatic During Pregnancy patients must be based on clinical judgment, it is reasonable to Knowledge of the cardiovascular changes of pregnancy is nec repeat echocardiography at a cumulative anthracycline dose of essary to distinguish betr,teen normal and pathologic signs and 250 mg/m2 and before each dose in patients with pre existing symptoms in the pregnant patient (Table 45). During a normal LV dysfunction or those receiving higher cumulative doses. pregnancy, patients develop a relative anemia due to increases The frequency of echocardiographic surveillance in patients in plasma volume and, to a lesser degree. erythrocyte mass. receiving trastuzumab who are at high risk for cardiac dys- Mean arterial pressure slightly decreases in the setting of function is based on clinical judgment. Trastuzumab is tempo reduced systemic vascular resistance and increased heart rate rarily stopped if the LVEF drops by more than 157, or drops and cardiac output. By the 32nd week ofpregnancy. maternal 10% to 15% and below the normal level. Patients who demon cardiac output peaks at approximately 407, to 50'X, above the strate normalization of LV function after discontinuation of prepregnancy level owing to increased heart rate and stroke trastuzumab may receive additional therapy, and retrospective volume. During delivery the cardiac output may increase to as data has shown that patients whose LVEF remains greater than much as BO'X, above the prepregnancy level. 50% may continue treatment without long term cardiac effects. A relative decline in GLS ofgreater than 15'7, is considered sub clinical LV dysfunction and should prompt consultation with a Prepreg na ncy Eval uation cardiologist. In patients taking sunitinib, surveillance with A1l women with cardiovascular disease should receive preg baseline N-terminal pro-B-type natriuretic peptide measure nancy counseling. If appropriate, women should receive ment and LVEF assessment at baseline, 1 month, and every genetic counseling and possibly testing. Women who are 3 months thereafter has been advocated. anticipating pregnancy should undergo multidisciplinary 114

I : Pregnancy and Cardiovascular Disease TABLE 45. Normal Versus Pathologic Signs and pulmonary hypertension, previous peripartum cardiomyopa Symptoms in Pregnancy thy with residual left'uentricular dysfunction, severe left ven Type of Sign or Normal Pathologic tricular dysfunction (ejection lraction <30'X, or New York Hearl Symptom Association functional class III IV sy,mptoms), severe mitral Pulmonary Mild dyspnea, Orthopnea, stenosis, symptomatic severe aortic stenosis, and marked dyspnea with paroxysmal ascending aorta dilatation. Care and delivery should be per exertion nocturnal dyspnea, formed at an expert center for pregnancy and cardiac disease. cough, pulmonary edema XEY POITTS Cardiac No symptoms Chest pressure, . Women with cardiovascular disease who are anticipat- heaviness, or pain ing pregnancy should undergo multidisciplinary Ed e m a Mild peripheral More than mild prepregnancy evaluat ion. edema edema o Cardiovascular conditions that confer an extremely Heart rhythm Atrial and Atrialfibrillation or ventricu la r flutter, ventricular high risk for maternal mortality or severe morbidilz premature beats tachycard ia include pulmonary hypertension, previous peripartum Heart rate Heart rate Heart rate >100/min cardiomyopathy with residual left ventricular dysfunc increased by tion, severe left ventricular dysfunction (ejection frac L 20%-30% tion <30% or New York Heart Association functional Blood pressure Blood pressure Low blood pressure class III IV symptoms), severe mitral stenosis, sympto- typically is associated with modestly symptoms, high matic severe aortic stenosis, and marked ascending decreased blood pressure aorta dilatation. (- 10 mm Hg) (>140 mm Hg systolic or >90 mm I Hg diastolic) Auscultatory Basal systolic Systolic murmur Management of Cardiovascular murmur grade grade >3/6, any 1/6 or 2/6 diastolic murmur, Sa Disease During Pregnancy present in 80% of Women with obstructive valvular lesions ntay experience pregnant women, 53 symptoms during pregnancy because of the resultant increases in blood volume and cardiac output. These patients should be evaluated to determine whether cardiac intenrention should be evaluation with a cardiologist, a maternal fetal medicine spe- considered before pregnancy. Women with regurgitant valve cialist, and an obstetric anesthesiologist to determine the risks lesions usually tolerate pregnancy well. Women with sympto- I

TABLE 45. Normal Versus Pathologic Signs and pulmonary hypertension, previous peripartum cardiomyopa Symptoms in Pregnancy thy with residual left'uentricular dysfunction, severe left ven Type of Sign or Normal Pathologic tricular dysfunction (ejection lraction <30'X, or New York Hearl Symptom Association functional class III IV sy,mptoms), severe mitral Pulmonary Mild dyspnea, Orthopnea, stenosis, symptomatic severe aortic stenosis, and marked dyspnea with paroxysmal ascending aorta dilatation. Care and delivery should be per exertion nocturnal dyspnea, formed at an expert center for pregnancy and cardiac disease. cough, pulmonary edema XEY POITTS Cardiac No symptoms Chest pressure, . Women with cardiovascular disease who are anticipat- heaviness, or pain ing pregnancy should undergo multidisciplinary Ed e m a Mild peripheral More than mild prepregnancy evaluat ion. edema edema o Cardiovascular conditions that confer an extremely Heart rhythm Atrial and Atrialfibrillation or ventricu la r flutter, ventricular high risk for maternal mortality or severe morbidilz premature beats tachycard ia include pulmonary hypertension, previous peripartum Heart rate Heart rate Heart rate >100/min cardiomyopathy with residual left ventricular dysfunc increased by tion, severe left ventricular dysfunction (ejection frac L 20%-30% tion <30% or New York Heart Association functional Blood pressure Blood pressure Low blood pressure class III IV symptoms), severe mitral stenosis, sympto- typically is associated with modestly symptoms, high matic severe aortic stenosis, and marked ascending decreased blood pressure aorta dilatation. (- 10 mm Hg) (>140 mm Hg systolic or >90 mm I Hg diastolic) Auscultatory Basal systolic Systolic murmur Management of Cardiovascular murmur grade grade >3/6, any 1/6 or 2/6 diastolic murmur, Sa Disease During Pregnancy present in 80% of Women with obstructive valvular lesions ntay experience pregnant women, 53 symptoms during pregnancy because of the resultant increases in blood volume and cardiac output. These patients should be evaluated to determine whether cardiac intenrention should be evaluation with a cardiologist, a maternal fetal medicine spe- considered before pregnancy. Women with regurgitant valve cialist, and an obstetric anesthesiologist to determine the risks lesions usually tolerate pregnancy well. Women with sympto- I of pregnancy and develop a management plan for labor and matic obstructive hypertrophic cardiomyopathy should be the postpartum period. Disease specific risk should be treated with nonvasodilating p blockers, with monitoring of assessed using the modified World Health Organization preg fetal growth. I

of pregnancy and develop a management plan for labor and matic obstructive hypertrophic cardiomyopathy should be the postpartum period. Disease specific risk should be treated with nonvasodilating p blockers, with monitoring of assessed using the modified World Health Organization preg fetal growth. I nancy risk classification (https:ilacademic.oup.com/view- Vaginal delivery is generally preferred fbr patients with largel186437995). which is currently the most accurate system cardiovascular disease because it results in less blood loss. of risk assessment. quicker recovery and lower risk for thrombosis than does Women wilh certain cardiovascular disorders, including cesarean delivery. Cesarean delivery is recommended for uncomplicated small patent ductus arteriosus. mild pulmo- obstetric reasons in women with severe decompensated car nary stenosis, and mitral valve prolapse, have no increased diovascular disease and in some patients with a n-rarkedly I morbidity or mortality. Similarly. pregnant patients with suc dilated aorta. In women receiving warf'arin therapy, cesarean cessfully repaired simple lesions (atrial or ventricular septal delivery is indicated to reduce the risk for f'etal intracranial defect, patent ductus arteriosus, or anomalous pulmonary hemorrhage because the t'etus is fully anticoagulated. I venous drainage) or isolated atrial or ventricular ectopic beats do weil. These patients can be cared lbr and deliver in a local Peripartum Cardiomyopathy , hospital. Peripartum cardiomyopathy is left ventricular systolic dys Small increased risk of maternal mortality or moderate lunction recognized towarcl the end of pregnancy or in the increase in morbidity is associated with an unrepaired atrial or months following delivery in the absence of another identifi ventricular septal defect, repaired tetralogy of Fallot, most able cause. Risk factors fbr peripartum cardiomyopathy arrhythmias (supraventricular arrhythmias), and Turner syn include multiparity, age older than 30 years, Black race, mul drome without aortic dilatation. Patients with these conditions tiletal pregnancy, gestational hypertension, preeclampsia, a also can be cared for and deliver in a local hospital setting. previous episode of peripartun.r cardiomyopathy, and tocolytic Cardiovascular conditions that confer an extremely high therapy (e.g., terbutaline). Patients with peripartum cardio risk for nraternal mortality or severe morbidity include myopathy should be co managed by a cardiologist.

nancy risk classification (https:ilacademic.oup.com/view- Vaginal delivery is generally preferred fbr patients with largel186437995). which is currently the most accurate system cardiovascular disease because it results in less blood loss. of risk assessment. quicker recovery and lower risk for thrombosis than does Women wilh certain cardiovascular disorders, including cesarean delivery. Cesarean delivery is recommended for uncomplicated small patent ductus arteriosus. mild pulmo- obstetric reasons in women with severe decompensated car nary stenosis, and mitral valve prolapse, have no increased diovascular disease and in some patients with a n-rarkedly I morbidity or mortality. Similarly. pregnant patients with suc dilated aorta. In women receiving warf'arin therapy, cesarean cessfully repaired simple lesions (atrial or ventricular septal delivery is indicated to reduce the risk for f'etal intracranial defect, patent ductus arteriosus, or anomalous pulmonary hemorrhage because the t'etus is fully anticoagulated. I venous drainage) or isolated atrial or ventricular ectopic beats do weil. These patients can be cared lbr and deliver in a local Peripartum Cardiomyopathy , hospital. Peripartum cardiomyopathy is left ventricular systolic dys Small increased risk of maternal mortality or moderate lunction recognized towarcl the end of pregnancy or in the increase in morbidity is associated with an unrepaired atrial or months following delivery in the absence of another identifi ventricular septal defect, repaired tetralogy of Fallot, most able cause. Risk factors fbr peripartum cardiomyopathy arrhythmias (supraventricular arrhythmias), and Turner syn include multiparity, age older than 30 years, Black race, mul drome without aortic dilatation. Patients with these conditions tiletal pregnancy, gestational hypertension, preeclampsia, a also can be cared for and deliver in a local hospital setting. previous episode of peripartun.r cardiomyopathy, and tocolytic Cardiovascular conditions that confer an extremely high therapy (e.g., terbutaline). Patients with peripartum cardio risk for nraternal mortality or severe morbidity include myopathy should be co managed by a cardiologist. 115

Pregnancy and Cardiovascular Disease Death in women with peripartum cardiomyopathy is Spontaneous coronary artery dissection is the leading caused by heart failure, thromboembolic events, or arrhyth- cause of pregnancy associated myocardial infarction and mias. Most women who develop peripartum cardiomyopathy occurs most commonly in the first month postpartum (see recover fully, as measured by improvement in ejection frac- Coronary Artery Disease). Conservative noninterventional tion; however, in a prospective study, 13%, had major cardiovas- therapy is preferred for most patients. cular events or persistent severe cardiomyopathy. Studies suggest that the time frame for recovery is 6 months. Prognostic Cardiovascular Medication Use factors that portend a worse outcome include severe Ieft ven- During Pregnancy tricular dysfunctionidilatation at presentation, Black race, Guidelines for the use of select cardiolascular drugs during older maternal age, and multiparity. pregnancy are outlined in Table 46. Most cardiovascular drugs Women with peripartum cardiomyopathy should be are not FDA-approved for use during pregnancy because of promptly treated with medical therapy that may include limited safety data. Cardiovascular medications should be B-blockers, digoxin, hydralazine, nitrates, and diuretics. ACE used only when needed and at the lowest possible dosage, inhibitors, angiotensin receptor blockers, and aldosterone with the desired therapeutic effect outweighing the risk. antagonists are teratogenic and should be avoided until after p-Blocker use during pregnancy or lactation requires peri delivery. Owing to the high risk lor thromboembolism associ- odic fetal and newbom heart rate monitoring because p-blockers ated with peripartum cardiomyopathy, anticoagulation is rec- cross the placenta and are present in human breast milk. ommended for women with left ventricular ejection fraction labetalol is the preferred B blocker in this setting. Atenolol has below 35'7,. The choice of anticoagulant (heparin or warfarin) been linked to premature delivery and small-for-gestational-age depends on whether the patient is still pregnant and the time babies and thus is usually avoided during pregnancy. since delivery. Duration of anticoagulation is at least 8 weeks, Adenosine is the drug of choice for treatment of acute although therapy can be discontinued sooner if the ejection symptomatic supraventricular tachycardia during pregnancy. fraction normalizes. Recurrent episodes of tachycardia are often treated with Women with severe refractory heart failure due to peri- p-blockers; sotalol and flecainide have also been used safely. partum cardiomyopathy should be referred to a specialty Because of toxicity concerns, amiodarone is used rarely. center for advanced treatment, including ventricular assist ACE inhibitors, angiotensin receptor blockers, direct device placement, advanced arrhythmia management, and renin inhibitors, and aldosterone antagonists should be heart transplantation. avoided during pregnancy, although some ACE inhibitors and Because subsequent pregnancy is often associated with spironolactone are safle to use while breastfeeding. There is recurrent or further reduction of left ventricular function, inconclusive evidence on the safety of direct renin inhibitors potentially resulting in clinical deterioration or death, women and angiotensin receptor blockers while breastfeeding; these with a previous episode of peripartum cardiomyopathy with drugs are generally avoided during lactation. persistent left ventricular dysfunction should be advised to A useful source of information on drugs to which breast- avoid future pregnancy. feeding mothers may be exposed, including potential adverse effects and suggested therapeutic alternatives, is the LactMed Other Cardiovascular Disorders database (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm). Data have linked adverse pregnancy outcomes (hypertensive disorders of pregnancy, preterm delivery glucose intolerance Anticoagulation Therapy During Pregnancy during pregnancy, small for gestational-age delivery placental Pregnancy is associated with hypercoagulability. Table 47 lists abruption, and pregnancy loss) with the acquisition of cardio- the indications for anticoagulation in pregnancy, recom vascular risk factors and cardiovascular disease. It is unknown mended regimens, and monitoring parameters for therapy. how this information should be used to reclassiflz cardiovascu- Prepregnancy counseling is recommended for all r.tomen lar risk in affected women, but a heart healthy diet and exer- requiring long-term anticoagulation to enable them to make cise are recommended beginning in the postpartum period informed decisions regarding anticoagulant preference and to and extending throughout the lifespan. understand the maternal and fetal risks. Women with Marfan syndrome and related conditions Warfarin, unfractionated heparin, and low molecular- have an increased risk for pregnancy related aortic dissection. weight heparin can all be used during pregnancy. Careful Aortic repair is recommended before pregnancy in women with monitoring and dosage adjustment to attain the therapeutic Marfan syndrome and an aortic diameter of 4.5 cm or greater. target are indicated for all anticoagulation regimens. Warfarin Risk factors for dissection in pregnant patients with Marfan use during the first trimester can cause warfarin embryopa syndrome and an aortic diameter smaller than 4.5 cm include thy; the risk is increased when the daily dose is greater than rapid dilatation of the aorta or a personal or family history of 5 mg. Warfarin is stopped before delivery owing to the risk for aortic dissection. Patients with risk factors and an ascending fetal intracranial hemorrhage ifspontaneous labor and vaginal aortic diameter greater than 4.0 cm should be counseled to delivery occur while the mother (and thus the fetus) is antico I undergo aortic valve repair or replacement before pregnancy agulated with warfarin.

Death in women with peripartum cardiomyopathy is Spontaneous coronary artery dissection is the leading caused by heart failure, thromboembolic events, or arrhyth- cause of pregnancy associated myocardial infarction and mias. Most women who develop peripartum cardiomyopathy occurs most commonly in the first month postpartum (see recover fully, as measured by improvement in ejection frac- Coronary Artery Disease). Conservative noninterventional tion; however, in a prospective study, 13%, had major cardiovas- therapy is preferred for most patients. cular events or persistent severe cardiomyopathy. Studies suggest that the time frame for recovery is 6 months. Prognostic Cardiovascular Medication Use factors that portend a worse outcome include severe Ieft ven- During Pregnancy tricular dysfunctionidilatation at presentation, Black race, Guidelines for the use of select cardiolascular drugs during older maternal age, and multiparity. pregnancy are outlined in Table 46. Most cardiovascular drugs Women with peripartum cardiomyopathy should be are not FDA-approved for use during pregnancy because of promptly treated with medical therapy that may include limited safety data. Cardiovascular medications should be B-blockers, digoxin, hydralazine, nitrates, and diuretics. ACE used only when needed and at the lowest possible dosage, inhibitors, angiotensin receptor blockers, and aldosterone with the desired therapeutic effect outweighing the risk. antagonists are teratogenic and should be avoided until after p-Blocker use during pregnancy or lactation requires peri delivery. Owing to the high risk lor thromboembolism associ- odic fetal and newbom heart rate monitoring because p-blockers ated with peripartum cardiomyopathy, anticoagulation is rec- cross the placenta and are present in human breast milk. ommended for women with left ventricular ejection fraction labetalol is the preferred B blocker in this setting. Atenolol has below 35'7,. The choice of anticoagulant (heparin or warfarin) been linked to premature delivery and small-for-gestational-age depends on whether the patient is still pregnant and the time babies and thus is usually avoided during pregnancy. since delivery. Duration of anticoagulation is at least 8 weeks, Adenosine is the drug of choice for treatment of acute although therapy can be discontinued sooner if the ejection symptomatic supraventricular tachycardia during pregnancy. fraction normalizes. Recurrent episodes of tachycardia are often treated with Women with severe refractory heart failure due to peri- p-blockers; sotalol and flecainide have also been used safely. partum cardiomyopathy should be referred to a specialty Because of toxicity concerns, amiodarone is used rarely. center for advanced treatment, including ventricular assist ACE inhibitors, angiotensin receptor blockers, direct device placement, advanced arrhythmia management, and renin inhibitors, and aldosterone antagonists should be heart transplantation. avoided during pregnancy, although some ACE inhibitors and Because subsequent pregnancy is often associated with spironolactone are safle to use while breastfeeding. There is recurrent or further reduction of left ventricular function, inconclusive evidence on the safety of direct renin inhibitors potentially resulting in clinical deterioration or death, women and angiotensin receptor blockers while breastfeeding; these with a previous episode of peripartum cardiomyopathy with drugs are generally avoided during lactation. persistent left ventricular dysfunction should be advised to A useful source of information on drugs to which breast- avoid future pregnancy. feeding mothers may be exposed, including potential adverse effects and suggested therapeutic alternatives, is the LactMed Other Cardiovascular Disorders database (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm). Data have linked adverse pregnancy outcomes (hypertensive disorders of pregnancy, preterm delivery glucose intolerance Anticoagulation Therapy During Pregnancy during pregnancy, small for gestational-age delivery placental Pregnancy is associated with hypercoagulability. Table 47 lists abruption, and pregnancy loss) with the acquisition of cardio- the indications for anticoagulation in pregnancy, recom vascular risk factors and cardiovascular disease. It is unknown mended regimens, and monitoring parameters for therapy. how this information should be used to reclassiflz cardiovascu- Prepregnancy counseling is recommended for all r.tomen lar risk in affected women, but a heart healthy diet and exer- requiring long-term anticoagulation to enable them to make cise are recommended beginning in the postpartum period informed decisions regarding anticoagulant preference and to and extending throughout the lifespan. understand the maternal and fetal risks. Women with Marfan syndrome and related conditions Warfarin, unfractionated heparin, and low molecular- have an increased risk for pregnancy related aortic dissection. weight heparin can all be used during pregnancy. Careful Aortic repair is recommended before pregnancy in women with monitoring and dosage adjustment to attain the therapeutic Marfan syndrome and an aortic diameter of 4.5 cm or greater. target are indicated for all anticoagulation regimens. Warfarin Risk factors for dissection in pregnant patients with Marfan use during the first trimester can cause warfarin embryopa syndrome and an aortic diameter smaller than 4.5 cm include thy; the risk is increased when the daily dose is greater than rapid dilatation of the aorta or a personal or family history of 5 mg. Warfarin is stopped before delivery owing to the risk for aortic dissection. Patients with risk factors and an ascending fetal intracranial hemorrhage ifspontaneous labor and vaginal aortic diameter greater than 4.0 cm should be counseled to delivery occur while the mother (and thus the fetus) is antico I undergo aortic valve repair or replacement before pregnancy agulated with warfarin. 116